P1149: THE EVOLVING STATE OF PLAY IN 1000 PATIENTS WITH WALDENSTRÖM’S MACROGLOBULINAEMIA IN THE UNITED KINGDOM (UK): A REAL-WORLD DATA ANALYSIS FROM THE WMUK RORY MORRISON REGISTRY PROJECT
Authors: E. Uppal, A. Otamas, J. Khwaja, H. McCarthy, J. Kothari, A. Rismani, D. El-Sharkawi, C. Kyriakou, S. D’Sa
Journal: HemaSphere (2022)

Background: Waldenström’s Macroglobulinaemia (WM) is a rare B-NHL, with an incidence of 0.55 per 100,000 per year in the UK (1). As novel therapies move from the bench to the clinic, real world data (RWD) is important to understand trends and supplement data from clinical trials. The Rory Morrison Registry (RMR) collects sequential data on diagnosis, treatment landscape and outlook for patients from 25 UK centres. Aims: To characterise therapy trends in the UK by an analysis of disease and treatment characteristics, and survival status. Methods: The RMR was searched for all patients with a diagnosis of WM. Information regarding demographics, disease characteristics, bone marrow (BM) results, treatment and survival status were collected retrospectively; the earliest diagnosis was in 1978 and the data lock was on 25/2/22. Results: 1007 patients with a diagnosis of WM using consensus criteria (2) at 25 UK Centres (94.5% academic, 5.5% district centres) were identified. The following data pertain to diagnosis; median age was 64 years (21-93); M:F ratio 1.6:1, 90% of white ethnicity. Diagnostic sub-entities included peripheral neuropathy (116), cryoglobulinaemia (68), amyloidosis (22), Bing-Neel syndrome (18) and Schnitzler’s syndrome (9); 53% (501/945) were symptomatic at diagnosis. The median IPSSWM for 496 patients was 2. MYD88 L265P by RT-PCR was found in 87.1% (304/349) and CXCR4 mutations in 28.9% (26/90). Of the total, 690 (68.5%) patients received treatment with a median time from diagnosis to first line (L1) treatment of 3 months (0-312). Indications for L1 were recorded as: 274/690 lymphoma related, 248/690 paraprotein-related, 65/690 B-Symptoms, 101/690 other indications. Regarding later lines, 402 (39.9%) patients received a 2nd treatment (L2); median time from end L1 to beginning of L2 was 15.1 months (0-163). A 3rd line (L3) was administered in 226 (22.4%) patients; median time from end of L2 to start of L3 was 9 months (0-158); 125 (12.4%) patients received ≥4 treatments. Between 1984 and 2021 the three most popular treatments received at L1 were: Dexamethasone-Rituximab-Cyclophosphamide (DRC) 20.1% (144/690), R-Bendamustine (BR) 15.2% (105/690), Fludarabine based (±Cyclophosphamide, Rituximab) 9.0% (62/690) [Figure 1]. The three most popular treatments at L2 were: Ibrutinib 24.9% (100/402), BR 9.5% (38/402), DRC 5.0% (20/402). Ibrutinib is the leading 2nd, 3rd, 4th line treatment option from 2018 across all centres, due to its availability on the national Cancer Drugs Fund from Nov 2017. The most received treatments from 2020 at: Ibrutinib 31.1% (60/193), R-Bendamustine 12.4% (24/193), DRC 10.4% (20/193). 38 patients underwent autologous and 7 allogeneic stem cell transplants between 2002 to 2020 at a median of L3 (range 1-7). At the time of data lock, 184 patients were labelled deceased. Cause of death was available for 78 patients: 15 due to WM, 7 patients high grade transformation, 3 amyloid, 3 during ASCT, 2 AML/MDS. Image:Summary/Conclusion: This RWD analysis of >1000 UK patients shows that inter/national consensus guidelines are resulting in more streamlined treatment approaches in WM. As targeted therapies have become available, there is a paradigm shift towards their use; however there is still much to learn about the optimal selection and sequencing of therapies in WM patients whose diseases are heterogenous by nature. Patient-related outcome studies are underway to complement ongoing follow-up of clinically meaningful remission duration and tolerance.